Neuropathy is a diseased condition of the nervous system. There are many types of neuropathy. Some examples of neuropathy include, but are not limited to, diabetic neuropathy, chemotherapy-induced peripheral neuropathy (CIPN) human immunodeficiency virus (HIV), and alcoholic neuropathy.
SGs are activated by sudomotor nerves. Neuropathy often affects these sudomotor nerves. One way of analyzing a neuropathic condition of a patient is to evaluate the patient's ability to sweat. The following sweat tests for diagnosing neuropathy are known.
The quantitative sudomotor axon reflex test (QSART) is the most common test. It tests the volume of water produced by SGs in a 1-2 sq. cm area of skin (sweat water/area). Testing begins by iontophoresis of acetylcholine (ACh) into a ring of skin to stimulate SGs in the ring to sweat maximally. The sudomotor nerves (axons) innervating the SGs are also excited. These axons propagate the excitatory impulses proximally that reach the spinal level. However, excitation also flows peripherally at axon branch points toward the skin and excites SGs in other areas of the skin including an area in the center circle of the device (this is the reflex). Air is passed over this center circle to pick up the water that is measured over time. Water is produced only during iontophoresis due to the short survival of acetylcholine in the body. The QSART is mainly used in research studies, and is discussed in the following paper: Low P A, Caskey P E, Tuck R R, Fealey R D, Dyck P J. Quantitative sudomotor axon reflex test in normal and neuropathic subjects. Annals of Neurology. 1983; 14:573-580.
Another sweat test is the silastic mold test. This test was described in the Kennedy lab. The silastic mold test stimulates maximal sweating by iontophoresis of pilocarpine, and measures the number of activated SGs and their approximate secretion volume. The sweating skin is wiped dry and the area is then quickly covered with silastic material. Sweat secreted from SGs pushes into and leaves an impression in the still soft silastic material before the silastic material completely dries. The silastic material drying time may be about 4 minutes. The dried silastic mold can be viewed through a microscope at low magnification by shining light through the mold. The thinned areas that were indented by the sweat drops look like holes. These holes are easily counted. The diameter of the holes may be measured to calculate approximate volume. Thus, the silastic mold test may be used to provide a count of all active SGs in the area of skin tested and the approximate size of sweat droplets. The number of active SGs decreases as neuropathy progresses. The silastic mold test is discussed in the following paper: Kennedy W R, Sakuta M, Quick D C. Rodent eccrine sweat glands: a case of multiple efferent innervation. Neuroscience [0306-4522] Kennedy, W R yr: 1984 vol: 11 iss: 3 pg: 741-749.
Another sweat test is the thermoregulatory test, which shows body areas that do not sweat when the body is heated, presumably because the nerves to the SGs in those areas have degenerated. The anterior body of the patient is dusted with an indicator powder containing alizarin red that turns from orange to purple when wet with sweat water. SGs in non-darkened skin are presumed to be unable to produce water because of nerve degeneration. The thermoregulatory test may be used to determine whether the patient is suffering from neuropathy and if so, where the neuropathy is located. The thermoregulatory test is discussed in the following paper: Fealey R D, Low P A, Thomas J E. Thermoregulatory sweating abnormalities in diabetes mellitus. Mayo Clin Proc. 1989 June; 64(6):617-28.
Another sweat test is the quantitative direct and indirect axon reflex testing (QDIRT) which evaluates sudomotor nerve function by measuring both the direct and axon-reflex mediated sweat response. SGs are stimulated by acetylcholine iontophoresis. A mixture of alizarin red, corn starch and sodium carbonate is quickly applied and digital photographs are taken 1/15 sec. for 7 min. It is difficult to avoid some evaporation. Sweat droplets are quantified by number, size and percent area over the area of interest, separating between direct and indirect sweat production. QDIRT is discussed in the following paper: Gibbons C H, Illigens B M, Centi J, Freeman R. QDIRT: quantitative direct and indirect test of sudomotor function. Neurology. 2008 Jun. 10; 70(24):2299-304. doi: 10.1212/01.wnl.0000314646.49565.c0. PMID: 18541883 [PubMed].
Another sweat test is the Dynamic Sweat Test (DST) developed by the Nolano lab in Italy and the Kennedy lab in Minnesota. The DST test may coat a sticky side of transparent tape with starch on the sticky side, and then place the tape onto the skin. The tape forces the sweat to spread laterally in a thin spot instead of a droplet. The edges of the dark spot are sharply imaged. The areas of the spots are measured at two times. The first time is just after tape is applied to the skin and the second time is when adjacent spots become confluent. If calibrated to known amounts of water, these two measurements can be used to manually calculate a change of a mean spot size over time (proportional to rate), mean sweat volume per cm2 skin and volume per skin area stimulated. The DST has minimal to no evaporation of the sweat, and also provides maximal stimulation over 40 minutes by using pilocarpine to stimulate the sweat. DST is discussed in the following paper: Provitera V, Nolano M, Caporaso G, Stancanelli A, Santoro L, Kennedy W R. Evaluation of sudomotor function in diabetes using the dynamic sweat test. Neurology. 2010 Jan. 5; 74(1):50-6. doi: 10.1212/WNL.0b013e3181c7da4b. PMID: 20038772
It is desirable to increase the accuracy of evaluating the peripheral nervous system in order to make an earlier diagnosis of peripheral neuropathy and to more sensitively evaluate the progression or improvement of the neuropathy. For example, it may be desirable to quantitatively show if a drug is helping or injuring individual patients at an early stage.